L. Legault et al., ASSESSMENT OF ATRIAL-NATRIURETIC-PEPTIDE RESISTANCE IN CIRRHOSIS WITHHEAD-OUT WATER IMMERSION AND ATRIAL-NATRIURETIC-PEPTIDE INFUSION, Canadian journal of physiology and pharmacology, 71(2), 1993, pp. 157-164
The nature of sodium retention in cirrhosis complicated by ascites has
been studied for the last 30 years. Resistance to the natriuretic act
ion of atrial natriuretic peptide (ANP) may play a potential role in t
his sodium retention. To further evaluate this possibility, we studied
12 patients with biopsy-proven cirrhosis and ascites on 2 consecutive
days after a 7-day period off diuretics while receiving a 20 mmol/day
sodium restricted diet. Following a crossover design, patients underw
ent head-out water immersion (HWI) for 3 h and were infused with a ce-
human ANP for 2 h on 2 consecutive days. Blood and urine samples were
collected hourly. Five patients displayed a natriuretic response to HW
I, sufficient to achieve negative sodium balance, and these patients w
ere termed responders. Each of these five patients also displayed a na
triuretic response to ANP infusion. In contrast, the other seven patie
nts (nonresponders) consistently failed to develop a natriuretic respo
nse to either maneuver. The two groups had similar elevations in plasm
a ANP concentrations, but at baseline differed in terms of plasma sodi
um, plasma renin activity, and serum aldosterone. Despite higher serum
aldosterone concentrations, nonresponders excreted less potassium tha
n responders during the peak effect of the interventions, suggesting g
reater sodium delivery to the aldosterone-sensitive nephron segment in
responders. We conclude that the inability to mount an adequate sodiu
m excretory response to HWI in patients with cirrhosis may be conveyed
through increased antinatriuretic factors that decrease the sodium de
livery to the medullary collecting duct and inhibit the natriuretic ef
fect of ANP at that site.